L-citrulline enriched fermented milk with Lactobacillus helveticus attenuates dextran sulfate sodium (DSS) induced colitis in mice.

Inflammatory bowel disease (IBD) is a group of chronic inflammatory gastrointestinal diseases that causes worldwide suffering. L. helveticus is a probiotic that can enhance intestinal barrier function via alleviation of excessive inflammatory response. Citrulline, a functional amino acid, has been reported to stimulate muscle synthesis and to function with a prebiotic-like action with certain Lactobacillus strains. The aim of this study was to investigate the potential synergistic effect of combining L. helveticus and citrulline on protection against damage induced by dextran sulfate sodium (DSS) in a mouse model. 6-week-old male C57BL/6J mice were fed with DSS water and randomly divided for administering with different milk treatments: 1) plain milk (control or DSS control), 2) 1% (w/v) citrulline enriched milk (Cit_milk), 3) milk fermented with L. helveticus (LHFM) and 4) DSS+milk fermented with L. helveticus with 1% (w/v) citrulline (Cit_LHFM). The treatment effects on the survival and macroscopic and microscopic signs were examined. All treatments presented different degrees of protective effects on attenuating the damages induced by DSS. All treatments reduced the body weight loss, disease activity index (DAI), histological scores, pro-inflammatory cytokine expression (IL-6, TNF-α and IFN-γ) and production (IL-4) (all P <0.05) and the tight junction (TJ) protein (zonula occluden-1 (ZO-1) expression. LHFM and Cit_LHFM improved survival rate (both at P<0.05). Particularly, Cit_LHFM showed greater effects on protecting the damages induced by DSS, especially in ameliorating colonic permeability, TJ protein (ZO-1, occludin and claudin-1) expression and distribution as well as in reducing IL-4 and IL-17 expression (all P <0.05). Our findings suggested that the combination of and citrulline had significant synergistic effect on protecting against injury from DSS-induced colitis. Therefore, citrulline enriched L. helveticus fermented milk is suggested to be a potential therapy for treating IBD.

Lupinus albus Protein Components Inhibit MMP-2 and MMP-9 Gelatinolytic Activity In Vitro and In Vivo.

Matrix metalloproteinases 2 and 9 (MMP-2 and MMP-9) are regarded as important clinical targets due to their nodal-point role in inflammatory and oncological diseases. Here, we aimed at isolating and characterizing am MMP-2 and-9 inhibitor (MMPI) from Lupinus albus and at assessing its efficacy in vitro and in vivo. The protein was isolated using chromatographic and 2-D electrophoretic procedures and sequenced by using MALDI-TOF TOF and MS/MS analysis. In vitro MMP-2 and 9 inhibitions were determined on colon adenocarcinoma (HT29) cells, as well as by measuring the expression levels of genes related to these enzymes. Inhibitory activities were also confirmed in vivo using a model of experimental TNBS-induced colitis in mice, with oral administrations of 15 mg·kg-1. After chromatographic and electrophoretic isolation, the L. albus MMP-9 inhibitor was found to comprise a large fragment from δ-conglutin and, to a lower extent, small fragments of ß-conglutin. In vitro studies showed that the MMPI successfully inhibited MMP-9 activity in a dose-dependent manner in colon cancer cells, with an IC50 of 10 µg·mL-1 without impairing gene expression nor cell growth. In vivo studies showed that the MMPI maintained its bioactivities when administered orally and significantly reduced colitis symptoms, along with a very significant inhibition of MMP-2 and -9 activities. Overall, results reveal a novel type of MMPI in lupine that is edible, proteinaceous in nature and soluble in water, and effective in vivo, suggesting a high potential application as a nutraceutical or a functional food in pathologies related to abnormally high MMP-9 activity in the digestive system.

Inhibitory effects of ß-type glycosidic polysaccharide from Pleurotus eryngii on dextran sodium sulfate-induced colitis in mice.

The aim of the present study was to determine the inhibitory effects and the potential underlying mechanisms of a novel Pleurotus eryngii ß-type glycosidic polysaccharide (WPEP) on colitis. To achieve this, sixty CD-1 (ICR) mice were divided into six groups including healthy and colitic mice treated with or without WPEP at two different doses (n = 10). The results showed that WPEP displayed a significant inhibitory effect on colitis as indicated by the lowered disease activity index in the treated colitic mice compared to the untreated colitic mice (2.78 ± 0.50 to 1.80 ± 0.17). A decrease in pro-inflammatory cytokine concentrations and pro-inflammatory protein expressions and an increase in the colon length (9.31 ± 0.59 cm to 10.89 ± 1.20 cm) along with histological improvements were also observed in the treated colitic mice compared to the untreated colitic mice in the present study. Flow cytometry and western blotting analysis revealed that these anti-colitis effects were associated with decreased accumulation of CD45+ immune cells, CD45 + F4/80+ macrophages and CD45 + Gr1+ neutrophils. Moreover, the 16s rRNA sequencing analysis of the gut microbiota revealed that WPEP partially reversed gut microbiota dysbiosis in the colitic mice including the decreased abundance of Akkermansia muciniphila (35.80 ± 9.10% to 18.24 ± 6.23%) and Clostridium cocleatum (2.34 ± 1.78% to 0.011 ± 0.003%) and the increased abundance of Bifidobacterium pseudolongum (3.48 ± 2.72% to 9.65 ± 3.74%), Lactobacillus reuteri (0.007 ± 0.002% to 0.21 ± 0.12%), Lactobacillus salivarius (1.23 ± 0.87% to 2.22 ± 1.53%) and Ruminococcus bromii (0.009 ± 0.001% to 3.83 ± 1.98%). In summary, our results demonstrated that WPEP could be utilized as a functional food component in colitis management as well as a potential prebiotic agent to improve inflammation-related disorders.

Orally Administered DHA-Enriched Phospholipids and DHA-Enriched Triglyceride Relieve Oxidative Stress, Improve Intestinal Barrier, Modulate Inflammatory Cytokine and Gut Microbiota, and Meliorate Inflammatory Responses in the Brain in Dextran Sodium Sulfate Induced Colitis in Mice.

SCOPE: Studies based on DHA/EPA supplementation in animal models of inflammatory bowel disease (IBD) reveal controversial results. It is speculated that different forms of DHA may explain the controversial results. Therefore, the effects of DHA-enriched phospholipids (DHA-PL) and DHA-enriched triglyceride (DHA-TG) on IBD are compared. METHODS AND RESULTS: Male C57BL6/J mice are given DHA-PL and DHA-TG for 14 consecutive days, and receive ad libitum a 3.0% dextran sodium sulfate solution on the eighth day to establish IBD model. The results show that both DHA-PL and DHA-TG can reverse the colitis pathological process by decreasing the disease activity indexes (DAI), raising the colon length, suppressing the intestinal permeability, suppressing the oxidative stress, down-regulating pro-inflammatory factors, up-regulating anti-inflammatory factor in colon tissues. DHA-PL and DHA-TG also regulate the composition of gut microbiota via decreasing of the abundance Bacteroidetes and Firmicutes, and DHA-TG increases the abundance of Odoribacter. Importantly, DHA-PL and DHA-TG obviously attenuate the activation of microglia. CONCLUSIONS: DHA-PL shows outstanding advantages in regulating oxidative stress, inflammatory responses, and intestinal barrier permeability. The current research indicates that the existence of DHA affects the improvement, DHA in phospholipid form could be a more effective choice for nutritional intervention to prevent and treat colitis.

Therapeutic and Prebiotic Effects of Five Different Native Starches on Dextran Sulfate Sodium-Induced Mice Model of Colonic Colitis.

SCOPE: The availability of studies related to the effects of natural macronutrients on inflammatory bowel disease (IBD) remain relatively limited. This study investigates whether and to what extent the consumption of five different native starches alleviate the clinical symptoms and dysbiosis of gut microbiota associated with colitis. METHODS AND RESULTS: Using dextran sodium sulfate (DSS)-induced mouse model of colitis, the potential effects of native potato starch (PS), pea starch (PEAS), corn starch (CS), Chinese yam starch (CYS), and red sorghum starch (RSS) on the clinical manifestations and dysbiosis of gut microbiota are studied. Compared to CS and RSS, the consumption of PEAS, PS, and CYS significantly diminishes clinical enteritis symptoms, including reduced disease activity index, and the alleviated degree of colonic histological damage. Furthermore, the analysis of gut microbiota reveals the significant prebiotic characteristics of PEAS, PS and CYS, as indicated by the maintenance of gut microbiota hemostasis and the inhibition of typically pathogenic bacteria, including Escherichia coli and Helicobacter hepaticus. CONCLUSION: Starches from potato, pea, and Chinese yam alleviate colitis symptoms in a mouse model, and also show significant prebiotic characteristics. These findings suggest a cost-effective and convenient dietary strategy for the management of IBD.

Diet and Inflammatory Bowel Disease: What Quality Standards Should Be Applied in Clinical and Laboratory Studies?

Many patients suffering from inflammatory bowel disease (IBD) follow restrictive diets, as many respective recommendations circulate. Efforts are made to evaluate and summarize the published information, for example, in a recent consensus manuscript by the International Organization for the Study of IBD (IOIBD). However, the standards that should be applied to make claims about dietary effects are poorly defined. In this manuscript, the scientific basis of recommendations for nutritional interventions in IBD is analyzed. Epidemiological evidence on diet in IBD is always biased by numerous factors, and the number of robust dietary intervention studies is limited due to methodological difficulties. Therefore, animal models are used to test hypotheses with respect to dietary factors and intestinal inflammation. Naturally, animal models have limitations, and knowledge of key characteristics of colitis animal models is crucial to understand their advantages and disadvantages. In recent years the important role of the microbiota for IBD and dietary factors has been discovered. Microbiota data are added to many publications on IBD and nutrition. The quality of those data varies largely. Subsequently, quality standards for microbiota analyses also are discussed. Finally, quality requirements to be applied on recommendations for dietary changes in patients with IBD are suggested.

Insufficient dietary choline aggravates disease severity in a mouse model of Citrobacter rodentium-induced colitis.

Dietary choline, which is converted to phosphatidylcholine (PC) in intestinal enterocytes, may benefit inflammatory bowel disease patients who typically have reduced intestinal choline and PC. The present study investigated the effect of dietary choline supplementation on colitis severity and intestinal mucosal homoeostasis using a Citrobacter rodentium-induced colitis model. C57BL/6J mice were fed three isoenergetic diets differing in choline level: choline-deficient (CD), choline-sufficient (CS) and choline-excess (CE) for 3 weeks prior to infection with C. rodentium. The effect of dietary choline levels on the gut microbiota was also characterised in the absence of infection using 16S rRNA gene amplicon sequencing. At 7 d following infection, the levels of C. rodentium in CD mice were significantly greater than that in CS or CE groups (P < 0·05). CD mice exhibited greater damage to the surface epithelium and goblet cell loss than the CS or CE mice, which was consistent with elevated pro-inflammatory cytokine and chemokine levels in the colon. In addition, CD group exhibited decreased concentrations of PC in the colon after C. rodentium infection, although the decrease was not observed in the absence of challenge. Select genera, including Allobaculum and Turicibacter, were enriched in response to dietary choline deficiency; however, there was minimal impact on the total bacterial abundance or the overall structure of the gut microbiota. Our results suggest that insufficient dietary choline intake aggravates the severity of colitis and demonstrates an essential role of choline in maintaining intestinal homoeostasis.

Intestinal release of biofilm-like microcolonies encased in calcium-pectinate beads increases probiotic properties of Lacticaseibacillus paracasei.

In this study, we show that calcium pectinate beads (CPB) allow the formation of 20 µm spherical microcolonies of the probiotic bacteria Lacticaseibacillus paracasei (formerly designated as Lactobacillus paracasei) ATCC334 with a high cell density, reaching more than 10 log (CFU/g). The bacteria within these microcolonies are well structured and adhere to a three-dimensional network made of calcium-pectinate through the synthesis of extracellular polymeric substances (EPS) and thus display a biofilm-like phenotype, an attractive property for their use as probiotics. During bacterial development in the CPB, a coalescence phenomenon arises between neighboring microcolonies accompanied by their peripheral spatialization within the bead. Moreover, the cells of L. paracasei ATCC334 encased in these pectinate beads exhibit increased resistance to acidic stress (pH 1.5), osmotic stress (4.5 M NaCl), the freeze-drying process and combined stresses, simulating the harsh conditions encountered in the gastrointestinal (GI) tract. In vivo, the oral administration of CPB-formulated L. paracasei ATCC334 in mice demonstrated that biofilm-like microcolonies are successfully released from the CPB matrix in the colonic environment. In addition, these CPB-formulated probiotic bacteria display the ability to reduce the severity of a DSS-induced colitis mouse model, with a decrease in colonic mucosal injuries, less inflammation, and reduced weight loss compared to DSS control mice. To conclude, this work paves the way for a new form of probiotic administration in the form of biofilm-like microcolonies with enhanced functionalities.

Elemental Diet Enriched with Amino Acids Alleviates Mucosal Inflammatory Response and Prevents Colonic Epithelial Barrier Dysfunction in Mice with DSS-Induced Chronic Colitis.

BACKGROUND: Clinical data suggest that enteral nutrition (EN) effectively decreases disease activity and maintains remission in patients with inflammatory bowel disease (IBD). However, the modulatory effects of EN on the intestinal mucosal immune system remain unclear. AIMS: This study first aimed at comparing the therapeutic effects of three EN formulas on ameliorating dextran sulfate sodium- (DSS-) induced chronic colitis; with the most effective formula, we then examined its influence on the mucosal inflammatory response and epithelial barrier function. METHODS: The effect of EN formulas on colitis in mice was assessed by body weight, disease activity index scores, colon length, and H&E staining for pathological examination. Colonic and circulating cytokine expression levels and the frequencies of immune cells were also analyzed. Intestinal epithelial barrier function was evaluated by detecting tight junction proteins. RESULTS: We found that among the three EN formulas, an elemental diet (ED) containing enriched amino acids restored the colitis-related reduction in body weight better than the other two EN formulas. ED amino acids suppressed the release of colonic proinflammatory mediators and maintained the expression of tight junction proteins in these mice. ED amino acid treatment mitigated the colitis-induced increase in CD103+CD11b+ dendritic cells and CD4+ and CD8+ T cells and inhibited the predominant Th1/Th17 responses particularly in the colonic mucosal lamina propria of mice with colitis. CONCLUSIONS: We showed that ED amino acids can be an effective immunomodulatory agent to reduce colitis-related inflammation by inhibiting proinflammatory mediators and Th1/Th17 cell responses and by repairing the disrupted epithelial barrier.

Menthacarin attenuates experimental colitis.

BACKGROUND: Peppermint oil and caraway oil are established remedies in gastroenterological medicine because of their spasmolytic/analgesic effects. PURPOSE: We investigated whether Menthacarin, a combination of both oils, exerted anti-inflammatory effects in a dextran sodium sulphate (DSS, 2%) murine model of colitis. STUDY DESIGN AND METHODS: C57BL/6 mice were orally administered Menthacarin in doses of 10, 30, 60, and 120 µg/g body weight (BW), and control mice received 0.2% agar, 10 µl/g BW, during 8 days of DSS-induced colitis. Colitis was monitored by BW measurements and colonoscopies. Colons of euthanised mice were excised for histological staining and ELISA measurements of the cytokines TNFα, IL-6, IL-10, IL-1ß, and TGF-ß. RESULTS: Menthacarin-treated mice compared to controls showed improved macroscopical and microscopical parameters and lower BW loss during the course of colitis. Menthacarin changed the colonic cytokine profile towards a regulatory/anti-inflammatory phenotype. CONCLUSION: Menthacarin attenuates experimental colitis and may be a promising add-on therapy for the treatment of IBD.

RETRACTED: Dietary oligosaccharides attenuate DSS-induced colitis in mice, induce PGlyRP3 expression, and inhibit NF-κB and MEK/ERK signaling.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the Editors. The Editors of Cellular Immunology have been informed by Elsevier that the article had been submitted to another journal while under consideration at "Cellular Immunology", which is a case of double submission. Based on the above infringement and its deleterious impact on the mutual trust necessary for the evaluation of scientific work - the corresponding authors had stated that the article was not submitted to another journal - it was decided to retract this article.

Effects of Linoleic Acid-Rich Diet on Plasma Profiles of Eicosanoids and Development of Colitis in Il-10-/- Mice.

Dietary intake of linoleic acid (LA, 18:2ω-6) has risen dramatically in recent decades. Previous studies have suggested a high intake of LA could increase tissue concentrations of proinflammatory and protumorigenic ω-6-series eicosanoid metabolites, increasing risks of inflammation and associated diseases. However, the effects of a LA-rich diet on in vivo profiles of eicosanoids and development of inflammatory diseases are understudied. Here, we treated spontaneous colitis-prone (Il-10-/-) mice with a control diet (∼3 Cal% LA) or a LA-rich diet (∼9 Cal% LA) for 18 weeks and analyzed the effects of the LA-rich diet on profiles of eicosanoids and development of colitis. We found that treatment with the LA-rich diet increased the tissue level of LA: the liver levels of LA were 5.8 ± 0.6% in the control diet-treated mice versus 11.7 ± 0.7% in the LA-rich diet-treated mice (P < 0.01). The plasma concentrations of a series of LA-derived metabolites, including 9-hydroxyoctadecadienoic acid (HODE), 9,10-dihydroxyoctadecenoic acid (DiHOME), 12,13-DiHOME, and 13-HODE were significantly increased by treatment with the LA-rich diet (P < 0.05). However, the LA-rich diet had little effect on the severity of colitis in the treated Il-10-/- mice. These results suggest a limited role of increased consumption of dietary LA on promoting colitis in the Il-10-/- model.

Effects of Vitamin D Supplementation on Inflammation, Colonic Cell Kinetics, and Microbiota in Colitis: A Review.

Vitamin D is widely known to regulate bone health, but there is increasing evidence that it may also ameliorate colitis through inflammation, cell proliferation and apoptosis, and the microbiota. The purpose of this review is to systematically examine the mechanisms by which vitamin D reduces colitis. PubMed and Web of Science were searched for articles published between 2008 and 2019 using key words such as "vitamin D," "colitis," "inflammatory bowel disease," "inflammation," "apoptosis," "cell proliferation," and "gut bacteria". Retrieved articles were further narrowed and it was determined whether their title and abstracts contained terminology pertaining to vitamin D in relation to colitis in human clinical trials, animal studies, and cell culture/biopsy studies, as well as selecting the best match sorting option in relation to the research question. In total, 30 studies met the established criteria. Studies consistently reported results showing that vitamin D supplementation can downregulate inflammatory pathways of COX-2, TNF-α, NF-κB, and MAPK, modify cell kinetics, and alter gut microbiome, all of which contribute to an improved state of colitis. Although vitamin D and vitamin D analogs have demonstrated positive effects against colitis, more randomized, controlled human clinical trials are needed to determine the value of vitamin D as a therapeutic agent in the treatment of colitis.

Consumption of a baked corn and bean snack reduced chronic colitis inflammation in CD-1 mice via downregulation of IL-1 receptor, TLR, and TNF-α associated pathways.

Ulcerative colitis (UC) is a condition that has been rising in the number of cases around the world. Food products made from natural ingredients such as corn and common bean might serve as alternatives for the treatment of UC. This study aimed to assess the anti-inflammatory effect of the consumption of a baked corn and bean snack (CBS) in an in vivo model of UC using 2% dextran sodium sulfate (DSS) as inductor of colitis. CD-1 mice (45, n = 9/group) were randomly separated into 5 groups, treated for 6-weeks as follows: G1 (basal diet, BD), G2 (2% DSS), G3 (20 g CBS/body weight BW/day + BD), G4 (40 g CBS/BW/day + BD) and G5 (60 g CBS/BW/day + BD). BW, Disease Activity Index (DAI), and feces were collected throughout the treatment. After euthanasia, organs (spleen, liver, and colon) were excised and weighed. Feces were analyzed for ß-glucuronidase (ß-GLUC) activity and gas-chromatography. The colons were analyzed for histopathology, myeloperoxidase (MPO) activity, and gene analysis. At the end of treatments, among the DSS-induced groups, G3 exhibited the lowest BW losses (11.5%), MPO activity (10.4%) and ß-GLUC (8.6%). G4 presented the lowest DAI (0.88), relative spleen weight, and histological inflammation score (p < 0.05). Compared to G2, CBS consumption significantly (p < 0.05) reduced serum TNF-α, IL-10, and MCP-1 levels. The fecal metabolome analysis ranked 9-decenoic acid, decane, and butyric acid as the main contributors of pathways associated with the ß-oxidation of fatty acids. G4 showed the highest fecal/cecal contents of short-chain fatty acids among all the DSS-induced groups. For the gene expression, G4 was clustered with G1, showing a differential inhibition of the pro-inflammatory genes Il1r1, Il1a, Tlr4, Tlr2, and Tnfrsf1b. In conclusion, CBS consumption decreased the inflammatory state and reduced the expression of the IL-1 receptor, TLR, and TNF-α-associated pathways in DSS-induced UC in CD-1 mice.

Hot-water extract of ripened Pu-erh tea attenuates DSS-induced colitis through modulation of the NF-κB and HIF-1α signaling pathways in mice.

Tea consumption has been found to be associated with low incidence of inflammatory bowel disease in Asian countries. However, there is very limited knowledge of such potential protection and its underlying mechanism. Ripened Pu-erh tea (RPT) belongs to the variety of microbial fermented tea, but its function regarding anti-inflammation remains unclear. In the present study, we investigated the effects of RPT on dextran sulfate sodium (DSS)-induced colitis in mice. The results demonstrated that RPT significantly relieved the loss of body weight, disease severity and shortening of colon length, and remarkably inhibited the secretion of pro-inflammatory cytokines by lessening the infiltration of inflammatory cells. Furthermore, we found that RPT suppressed the activation of the NF-κB pathway and down-regulated the expression of HIF-1α. Thus, it was concluded that RPT attenuated the progress of colitis via suppressing the HIF-1α/NF-κB signaling pathways thus reducing inflammation. This suggests that RPT may be a potential anti-inflammatory nutraceutical for the prevention and treatment of colonic colitis.

Dairy Propionibacterium freudenreichii ameliorates acute colitis by stimulating MUC2 expression in intestinal goblet cell in a DSS-induced colitis rat model.

An intact mucus layer is important in managing inflammatory bowel disease (IBD). Dairy Propionibacterium freudenreichii has probiotic potential, produces propionic acid and is known to promote health. The aim of this study was to evaluate the effects of P. freudenreichii on the improvement of colitis. LS 174T goblet cells and a dextran sodium sulfate (DSS)-induced colitis rat model were used to investigate the P. freudenreichii-induced stimulation of mucin production in vitro and in vivo, respectively. The mRNA and protein expression levels of MUC2, a main component of intestinal mucus, increased in the supernatant of P. freudenreichii culture (SPFC)-treated LS 174 cells. The SPFC and live P. freudenreichii (LPF) reduced the disease activity index (DAI) in the rats with DSS-induced colitis. After treatment with SPFC or LPF, the mRNA levels of typical pro-inflammatory cytokines decreased and the inflammatory state was histologically improved in the rats with DSS-induced colitis. The SPFC and LPF treatments increased the gene and protein expression levels of MUC2 in the rats with DSS-induced colitis compared with the expression levels in the negative control rats, and immunohistochemistry (IHC) showed an increase of the intestinal MUC2 level. In addition, SPFC and LPF augmented the level of propionate in the faeces of the rats with DSS-induced colitis. In conclusion, P. freudenreichii might improve acute colitis by restoring goblet cell number and stimulating the expression of MUC2 in intestinal goblet cells.

Plant- and Fish-Derived n-3 PUFAs Suppress Citrobacter Rodentium-Induced Colonic Inflammation.

SCOPE: Marine-derived n-3 PUFAs may ameliorate inflammation associated with inflammatory bowel diseases. Plant-derived n-3 PUFAs are thought to be inferior owing to shorter chain lengths. The aim of this study is to compare the impact of plant- and fish-derived PUFAs on murine colitis. METHODS AND RESULTS: C57BL/6 mice are fed high fat (36% kcal) diets with either 2.5% w/w sunflower oil (SO), flaxseed oil (FSO), ahiflower oil (AO), or fish oil (FO). After 4 weeks, mice are orogastrically challenged with Citrobacter rodentium (108 CFU) or sham gavaged. Fecal shedding is assayed at 2, 7, 10, and 14 days post infection (PI), and fecal microbiota at 14 days PI. Colonic inflammation and lipid mediators are measured. Supplementation regulates intestinal inflammation with crypt lengths being 66, 73, and 62 ±17 µm shorter (compared to SO) for FSO, AO, and FO respectively, p < 0.01. FSO blunts pathogen shedding at the peak of infection and FSO and AO both enhance fecal microbial diversity. FO attenuates levels of lipoxin and leukotriene B4 while plant oils increase pro-resolving mediator concentrations including D, E, and T-series resolvins. CONCLUSION: Plant and fish n-3 PUFAs attenuate colitis-induced inflammation while exhibiting characteristic pro-resolving lipid mediator metabolomes. Plant oils additionally promote microbial diversity.

Apple polysaccharide protects ICR mice against colitis associated colorectal cancer through the regulation of microbial dysbiosis.

The study tried to investigate whether apple polysaccharide (AP) could prevent colitis associated colorectal cancer (CACC) through the regulation of intestinal microbiota disorders. 10 % AP (w/v) was administrated to ICR mice by gavage for 15 wk. It was found that AP treatment protected against CACC in mice effectively. The level of Lactobacillus in the intestine of AOM/DSS-treated mice was significantly decreased and that of Fusobacterium increased; while AP could reverse this trend and increase the intestinal microbiota diversity. The number of T cells and macrophages in the colon tissue of mice in AOM/DSS group elevated; while AP could reduce the number of these cells significantly. AP suppressed nuclear aggregation of ß-catenin, inhibited the activation of Wnt pathway in colon tissues. These data suggest that AP prevented ICR mice from CACC at least in part through regulating intestinal flora disorder and Wnt pathway.

Dietary resveratrol attenuated colitis and modulated gut microbiota in dextran sulfate sodium-treated mice.

Accumulating evidence suggests that the gut microbiota plays an important role in the pathogenesis of colitis and that its composition could be modulated by exposure to dietary components. Thus, it may be possible to ameliorate the severity of colitis through administration of dietary components. Herein, we determined the effects of orally administered resveratrol on the gut microbiota composition and the resulting inflammatory status of a dextran sodium sulfate (DSS)-induced colitis mouse model. Our results supported our hypothesis that dietary resveratrol altered the microbial composition and restored microbial community diversity in DSS-treated mice. Specifically, resveratrol effectively decreased the abundance of the genera Akkermansia, Dorea, Sutterella and Bilophila, and increased the proportion of Bifidobacterium in colitic mice. Resveratrol was also able to prevent mouse body weight loss, reduce the disease activity index, attenuate tissue damage, and down-regulate the expression of pro-inflammatory cytokines such as IL-2, IFN-γ, GM-CSF, IL-1ß, IL-6, KC/GRO, and TNF-α in the colon of DSS-treated mice. Pearson's correlation analysis indicated significant correlations between the relative levels of these pro-inflammatory cytokines and alterations of the gut microbiota. Our results demonstrated that dietary resveratrol attenuated the inflammatory status and alleviated gut microbiota dysbiosis in a colitis mouse model.

Beneficial Effects of Oat Beta-Glucan Dietary Supplementation in Colitis Depend on its Molecular Weight.

BACKGROUND: Inflammatory bowel diseases are an important health problem. Therefore, the aim of the present study was to compare the impact of isolated oat beta-glucan fractions of low and high molecular weight, taken as dietary supplementation, on inflammatory markers in the colitis model. METHODS: Two groups of Sprague-Dawley rats-control and with experimentally induced colitis-were subsequently divided into three subgroups and fed over 21 days feed supplemented with 1% of low (ßGl) or high (ßGh) molecular weight oat beta-glucan fraction or feed without supplementation. The level of colon inflammatory markers, cytokines, and their receptors' genes expressions and immune cells numbers were measured by ELISA, RT-PCR, and by flow cytometry methods, respectively. RESULTS: The results showed moderate inflammation affecting the colon mucosa and submucosa, with significant changes in the number of lymphocytes in the colon tissue, elevated cytokines and eicosanoid levels, as well as disruption of the main cytokine and chemokine cell signaling pathways in colitis rats. Beta-glucans supplementation caused a reverse in the percentage of lymphocytes with stronger effects of ßGh and reduction of the levels of the inflammatory markers, and improvement of cytokine and chemokine signaling pathways with stronger effects of ßGl supplementation. CONCLUSIONS: The results indicate the therapeutic effect of dietary oat beta-glucan supplementation in the colitis in evident relation to the molecular weight of polymer.